CDK4/6 inhibition and sorafenib: a menage a deux in HCC therapy?

Hepatocytes are the foreign legionnaires in our body. They are exposed to various xenobiotics, which invigorates them and when transformed into malignant cells, renders them drug resistant. So far, treatment with the multikinase inhibitor sorafenib, which blocks Raf, vascular endothelial growth factor receptor and platelet-derived growth factor receptor signalling, is the only approved targeted therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib extends the average life expectancy of patients only 2.8 months over the placebo,1 which offers room for improvement. Unfortunately, several other drugs and combinatorial therapies, such as sorafenib plus erlotinib failed in clinical trials.1 2 In this issue of Gut, Bollard et al3 tested the combination of sorafenib with palbociclib in preclinical HCC mouse models. Palbociclib (or PD0332991) is a reversible and orally bioavailable low-molecular-weight cyclin-dependent kinase (CDK)4/6 inhibitor without significant off-target effects.4 The history of palbociclib is...
Source: Gut - Category: Gastroenterology Authors: Tags: Commentary Source Type: research

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The incidence of human papillomavirus–positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surpassed that of cervical cancer and is projected to increase rapidly until 2060. The coevolution of HPV with transforming epithelial cells leads to the shutdown of host immune detection. Targeting proximal viral nucleic acid–sensing machinery is an evolutionarily conserved strategy among viruses to enable immune evasion. However, E7 from the dominant HPV subtype 16 in HNSCC shares low homology with HPV18 E7, which was shown to inhibit the STING DNA-sensing pathway. The mechanisms by which HPV16 suppresses S...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Authors: He H, Li PC, Jia W, Hu B, Ji CS Abstract BACKGROUND Recently, targeted therapy for malignant tumors has developed rapidly, but there is still no effective targeted therapy for advanced esophageal squamous cell carcinoma (ESCC). Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a key enzyme involved in folate metabolism and is closely related to the proliferation in many cancers. However, few studies have explored the expression of MTHFD2 in ESCC and its prognostic significance. MATERIAL AND METHODS The expressions of MTHFD2, ki67, and p53 in ESCC tissues were detected by immunohistochemistry. Further, ...
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Publication date: Available online 24 February 2020Source: Respiratory Medicine Case ReportsAuthor(s): Takayasu Ito, Shotaro Okachi, Tadasuke Ikenouchi, Futoshi Ushijima, Takamasa Ohashi, Masahiro Ogawa, Masato Nagahama, Keiko Wakahara, Naozumi HashimotoAbstractA 65-year-old man with chronic respiratory failure caused by chronic obstructive pulmonary disease, had a pulmonary nodule adjacent to the inlet of right B1 and B3. The patient had undergone a surgery for right renal cell carcinoma and colon cancer 6 years prior. We attempted endobronchial ultrasound-guided transbronchial needle aspiration under non-invasive positiv...
Source: Respiratory Medicine Case Reports - Category: Respiratory Medicine Source Type: research
Conditions:   Recurrent Head and Neck Squamous Cell Carcinoma;   Head and Neck Cancer Stage IV Interventions:   Drug: Nivolumab + Paclitaxel;   Drug: Cetuximab + Paclitaxel Sponsors:   Grupo Español de Tratamiento de Tumores de Cabeza y Cuello;   Bristol-Myers Squibb;   Apices Soluciones S.L. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Nasopharyngeal Carcinoma Intervention:   Drug: SHR-1701 Sponsor:   Jiangsu HengRui Medicine Co., Ltd. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Solid Tumor, Adult;   Triple Negative Breast Cancer;   Colorectal Cancer;   Hepatocellular Carcinoma;   Osteosarcoma;   Epithelial Ovarian Cancer;   Gastric Cancer Intervention:   Biological: CRX100 suspension for infusion Sponsor:   BioEclipse Therapeutics Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Rectal Adenocarcinoma;   Rectum Neoplasm;   Rectum Carcinoma;   Colorectal Cancer;   Colorectal Neoplasms;   Colorectal Carcinoma;   Surgical Site Infection;   Surgery--Complications Interventions:   Drug: Oral Antibiotics;   Drug: Placebo;   Drug: Mechanical Bowel Preparation Sponsor:   Helsinki University Central Hospital Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionsIn patients with stage III/IV, ECOG-PS 2 or greater, and/or G8 score less than 11.5, treatment was difficult, and the prognosis was poor.
Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology - Category: ENT & OMF Source Type: research
AbstractThree BODIPY ‐peptide conjugates designed to target the epidermal growth factor receptor (EGFR) at the extracellular domain were synthesized and their specificity for binding to EGFR was investigated. Peptide sequences containing seven amino acids, GLARLLT (2) and KLARLLT (3), and 13 amino acids, GYHWYGYTPQNVI (4), were conjugated to carboxyl BODIPY dye (1) by amide bond formation in up to 73% yields. The BODIPY ‐peptide conjugates and their “parent” peptides were determined to bind to EGFR experimentally using SPR analysis, and were further investigated using computational methods (AUTODOCK). Resul...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: SPECIAL ISSUE RESEARCH ARTICLE Source Type: research
Authors: Rossi RE, Monteleone M, Altomare M, Cattaneo L, Torchio M, Coppa J, Mazzaferro V PMID: 32083410 [PubMed - as supplied by publisher]
Source: Minerva Chirurgica - Category: Surgery Tags: Minerva Chir Source Type: research
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